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Post-transcriptionally regulated genes are essential for pluripotent stem cell survival

Iwasaki, M.; Kawahara, Y.; Tabata, T.; Nishi, Y.; Narita, M.; Ohta, A.; Saito, H.; Yamamoto, T.; Nakagawa, M.; Yamanaka, S.; Takahashi, K.

2021-10-19 molecular biology
10.1101/2021.10.18.462967 bioRxiv
Show abstract

The effects of transcription factors on the maintenance and differentiation of pluripotent stem cells (PSCs) have been well studied. However, the importance of post-transcriptional regulatory mechanisms, which cause the quantitative dissociation of mRNA and protein expression, has not been explored in detail. Here, by combining transcriptome and proteome profiling, we identified 228 post-transcriptionally regulated genes with strict upregulation of the protein level in PSCs. Among them, we found that 84 genes were vital for the survival of PSCs and HDFs, including 20 genes that were specifically necessary for the survival of PSCs. These 20 proteins were upregulated only in PSCs and not in differentiated cells derived from the three germ layers. Subcellular fractionation of the mRNA showed that the expression of most of the 20 proteins was regulated at the mRNA localization stage from the nucleus to the cytoplasm, but their translation efficiency was constant. Together, these results revealed that post-transcriptionally regulated genes have a crucial role in PSC survival.

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